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2001 Progress Report: Mechanisms of Toxicity of Particulate Matter Using Transgenic Mouse Strains

EPA Grant Number: R827355C005
Subproject: this is subproject number 005 , established and managed by the Center Director under grant R827355
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Airborne PM - Northwest Research Center for Particulate Air Pollution and Health
Center Director: Koenig, Jane Q.
Title: Mechanisms of Toxicity of Particulate Matter Using Transgenic Mouse Strains
Investigators: Luchtel, Daniel L. , Baker, Coralie , Farin, Fred , Kavanagh, Terry
Current Investigators: Luchtel, Daniel L. , Baker, Coralie , Ceballos, Diana , Kavanagh, Terry , Leaman, Susan , McConnachie, Lisa , Rosenfeld, Michael
Institution: University of Washington , Washington State University
Current Institution: University of Washington
EPA Project Officer: Stacey Katz/Gail Robarge,
Project Period: June 1, 1999 through May 30, 2004 (Extended to May 31, 2006)
Project Period Covered by this Report: June 1, 2001 through May 30, 2002
Project Amount: Refer to main center abstract for funding details.
RFA: Airborne Particulate Matter (PM) Centers (1999)
Research Category: Particulate Matter

Description:

Objective:

The objective of this research project is to test the hypothesis that inhaled particulate matter (PM) causes the release of inflammatory mediators from cells in the lung that become bloodborne and target the cardiovascular system, particularly the heart. The project will use transgenic mouse strains with specific cardiovascular genetic alterations to address the research need to identify potential health conditions that enhance susceptibility to adverse PM health effects.

Progress Summary:

We have used a transgenic apolipoprotein E deficient (apoE-/-) mouse to study potential cardiovascular health effects of PM exposure. Physiological monitoring of heart rate/blood pressure or electrocardiogram (ECG) is conducted using implanted radio telemetry. Initial studies have used oropharyngeal aspiration of 125 µg of either SRM #1649 (Washington DC dust) or SRM #1648 (St. Louis dust). The protocols included monitoring a 24-hour baseline and then exposing the mice to either saline control or the dust in saline. Three of the studies used each animal as its own control, and one was a crossover design where two groups of mice were compared.

Heart rate was reduced and blood pressure was increased subsequent to PM exposure, although these changes at 24 hours were not notably different from the control mice. However, when the cardiovascular outcomes were examined hour by hour, a significant difference was observed 7 hours post exposure. This suggests that a short-term relationship may exist between cardiac events and PM exposure, as was seen in our heart rate variability measurements in panel subjects and in the myocardial infarction onset results in the Peters, et al., 2001 study.

Figure 1. ApoE-/- Mice Exposed to SRM # 1649: Heart Rate.

Future Activities:

Tissue samples of heart and lung with and without PM exposure are being prepared for genetic analysis using microarrays to look for differential expression of genes known to be involved in cardiovascular disease. This work is in collaboration with the Biomarker Core at the Center for Ecogenetics and Environmental Health.

Journal Articles:

No journal articles submitted with this report: View all 8 publications for this subproject

Supplemental Keywords:

particulate matter, PM, ambient particles, fine particles, combustion, health, exposure, biostatistics, susceptibility. , Air, Scientific Discipline, Health, Toxicology, Risk Assessments, Health Risk Assessment, Epidemiology, air toxics, Atmospheric Sciences, Biochemistry, particulate matter, Environmental Chemistry, aerosols, exposure assessment, exposure and effects, ambient air quality, cardiovascular disease, health effects, inhalation, mortality, hazardous air pollutants, atmospheric aerosols, cardiopulmonary responses, human health risk, particle exposure, mortality studies, air pollutants, human health effects, particulates, ambient particle health effects, air pollution, atmospheric chemistry, exposure, ambient aerosol, human exposure, morbidity, animal model

Progress and Final Reports:
1999 Progress Report
2000 Progress Report
Original Abstract
2002 Progress Report
2003 Progress Report
2004 Progress Report
Final Report


Main Center Abstract and Reports:
R827355    Airborne PM - Northwest Research Center for Particulate Air Pollution and Health

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R827355C001 Epidemiologic Study of Particulate Matter and Cardiopulmonary Mortality
R827355C002 Health Effects
R827355C003 Personal PM Exposure Assessment
R827355C004 Characterization of Fine Particulate Matter
R827355C005 Mechanisms of Toxicity of Particulate Matter Using Transgenic Mouse Strains
R827355C006 Toxicology Project -- Controlled Exposure Facility
R827355C007 Health Effects Research Core
R827355C008 Exposure Core
R827355C009 Statistics and Data Core
R827355C010 Biomarker Core
R827355C011 Oxidation Stress Makers

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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